Macular dystrophies associated with Stargardt-like phenotypes / Distrofias maculares associadas a fenótipos Stargardt-like

ABSTRACT Purpose: Stargardt-like phenotype has been described as associated with pathogenic variants besides the ABCA4 gene. This study aimed to describe four cases with retinal appearance of Stargardt disease phenotypes and unexpected molecular findings. Methods: This report reviewed medical records of four patients with macular dystrophy and clinical features of Stargardt disease. Ophthalmic examination, fundus imaging, and next-generation sequencing were performed to evaluate pathogenic variants related to the phenotypes. Results: Patients presented macular atrophy and pigmentary changes suggesting Stargardt disease. The phenotypes of the two patients were associated with autosomal dominant inheritance pattern genes (RIMS1 and CRX) and in the other two patients were associated with recessive dominant inheritance pattern genes (CRB1 and RDH12) with variants predicted to be pathogenic. Conclusion: Macular dystrophies may have phenotypic similarities to Stargardt-like phenotype associated with other genes besides the classic ones.

RESUMO Objetivo: Fenótipos Stargardt-like já foram asso-ciados a variantes patogênicas no gene ABCA4. O propósito desse estudo é descrever quatro pacientes com achados retinianos semelhantes a doença de Stargardt com resultados moleculares diferentes do esperado. Métodos: Esse relato fez a revisão de prontuários médicos de quatro pacientes com distrofia macular e achados clínicos sugestivos de doença de Stargardt. Foram realizados avaliação oftalmológica, exames de imagens e testes usando next generation sequencing para avaliar variantes patogênicas associadas aos fenótipos dos pacientes. Resultados: Os pacientes apresentavam atrofia macular e alterações pigmentares sugerindo achados clínicos de doença de Stargardt. Dois pacientes foram associados a genes com herança autossômica dominante (RIMS1 e CRX) e dois pacientes foram associados a genes com herança autossômica recessiva (CRB1 e RDH12) com variantes preditoras de serem patogênicas. Conclusão: Distrofias maculares podem ter similaridades fenotípicas com fenótipo de Stargardt-like associados a outros genes além dos classicamente já descritos.

Antiangiogenic activity of photobiomodulation in experimental model using chorioallantoic embryonic membrane of chicken eggs / Atividade antiangiogênica da fotobiomodulação em modelo experimental usando membrana embrionária corioalantóide de ovos de galinhas

ABSTRACT Purpose: The purpose of this study was to investigate the vascular effects of photobiomodulation using a light-emitting diode on the chorioallantoic embryonic membrane of chicken eggs grouped into different times of exposure and to detect the morphological changes induced by the light on the vascular network architecture using quantitative metrics. Methods: We used a phototherapy device with light-emitting diode (670 nm wavelength) as the source of photobiomodulation. We applied the red light at a distance of 2.5 cm to the surface of the chorioallantoic embryonic membrane of chicken eggs in 2, 4, or 8 sessions for 90 s and analyzed the vascular network architecture using AngioTool software (National Cancer Institute, USA). We treated the negative control group with 50 μl phosphate-buffered-saline (pH 7.4) and the positive control group (Beva) with 50 μl bevacizumab solution (Avastin, Produtos Roche Químicos e Farmacêuticos, S.A., Brazil). Results: We found a decrease in total vessel length in the Beva group (24.96% ± 12.85%) and in all the groups that received 670 nm red light therapy (2× group, 34.66% ± 8.66%; 4× group, 42.42% ± 5.26%; 8× group, 38.48% ± 6.96%), compared with the negative control group. The fluence of 5.4 J/cm2 in 4 sessions (4×) showed more regular vessels. The number of junctions in the groups that received a higher incidence of 670 nm red light (4× and 8×) significantly decreased (p<0.0001). Conclusion: Photo-biomodulation helps reduce vascularization in chorioallantoic embryonic membrane of chicken eggs and changes in the network architecture. Our results open the possibility of future clinical studies on using this therapy in patients with retinal diseases with neovascular components, especially age-related macular degeneration.

RESUMO Objetivo: investigar os efeitos vasculares da foto-biomodulação com diodo emissor de luz utilizando membrana embrionária corioalantóide de ovos de galinhas em grupos com diferentes tempos de exposição e detectar as alterações morfológicas por meio de métricas quantitativas promovidas pela luz na arquitetura da rede vascular. Métodos: Um aparelho de fototerapia com diodo emissor de luz no comprimento de onda de 670 nm foi usado como fonte de fotobiomodulação. A luz vermelha foi aplicada a uma distância de 2,5 cm da superfície da membrana embrionária corioalantóide em 2, 4 ou 8 sessões de 90 s a arquitetura da rede vascular foi analisada por meio do software AngioTool (National Cancer Institute, USA). Usamos um grupo controle negativo tratado com 50 µL de solução salina tamponada com fosfato (PBS) pH 7,4 e um grupo controle positivo (Beva) tratado com 50 µL de solução de bevacizumabe (Avastin, Produtos Roche Químicos e Farmacêuticos S.A., Brasil). Resultados: Uma diminuição no comprimento total do vaso foi detectada para o grupo Beva (24,96 ± 12,85%), e para todos os grupos que receberam terapia de luz vermelha de 670 nm, 34,66 ± 8,66% (2x), 42,42 ± 5,26% (4x) e 38,48 ± 6,96% (8x) em comparação ao grupo controle. A incidência de 5,4 J/cm2 em 4 sessões (4x) mostrou vasos mais regulares. A redução foi mais intensa nos grupos que receberam maior incidência de luz vermelha de 670 nm (4x e 8x). Conclusão: A fotobiomodulação contribui para a redução da vascularização nos vasos da membrana embrionária corioalantóide de ovos de galinhas e mudanças na arquitetura da rede. Os achados deste experimento abrem a possibilidade de considerar um estudo clínico usando esta terapia em pacientes com doenças retinais com componentes neovasculares, especialmente degeneração macular relacionada à idade.

PRPH2 mutation c.582-1G>A causing adult-onset macular dystrophy with a benign concentric annular macular dystrophy phenotype in a family / Mutação c.582-1G>A do gene PRPH2 causando distrofia macular de início adulto com fenótipo de distrofia macular anular concêntrica benigna em uma família

ABSTRACT The peripherin gene (PRPH2) mutation is associated with photoreceptor cell dysfunction as well as in several inherited retinal dystrophies. The PRPH2 mutation c.582-1G>A is a rare variant reported in retinitis pigmentosa and pattern dystrophy. Here Case 1 was of a 54-year-old woman with bilateral atrophy of the perifoveal retinal pigmentary epithelium and choriocapillaris with central foveolar respect. Autofluorescence and fluorescein angiography revealed perifoveal atrophy of the retinal pigmentary epithelium with an annular window effect without the "dark choroid" sign. Case 2 (mother of Case 1) presented with extensive atrophy of the retinal pigmentary epithelium and choriocapillaris. PRPH2 was evaluated and the c.582-1G>A mutation was identified in heterozygosity. An advanced adult-onset benign concentric annular macular dystrophy diagnosis was thereby proposed. The c.582-1G>A mutation is poorly known and not present in all common genomic databases. This case report is the first one to report a c.582-1G>A mutation associated with benign concentric annular macular dystrophy.

RESUMO Mutações do gene da periferina (PRPH2) estão associadas à disfunção das células fotorreceptoras e estão envolvidas em várias distrofias retinianas hereditárias. A mutação c.582-1G>A do gene PRPH2 é uma variante rara, relatada na retinite pigmentosa e nas distrofias em padrão. O caso 1 foi de uma mulher de 54 anos com atrofia bilateral do epitélio pigmentar da retina perifoveal e da coriocapilar, com acometimento foveolar central. A autofluorescência e a angiofluoresceinografia revelaram atrofia perifoveal do epitélio pigmentar da retina, com efeito de janela anular, sem o sinal da "coroide escura". O caso 2 (mãe) apresentava extensa atrofia do epitélio pigmentar da retina e da coriocapilar. Foi feito um estudo do gene PRPH2, que identificou a mutação c.582-1G>A em heterozigose. Foi proposto um diagnóstico de distrofia macular anular concêntrica benigna de início adulto em estágio avançado. A mutação c.582-1G>A é pouco conhecida e não está presente em todos os bancos de dados genômicos usuais. Este é o primeiro relato de caso publicado de uma mutação c.582-1G>A associada à distrofia macular anular concêntrica benigna.

Clinical features of patients with hepatolenticular degeneration aged above 35 years / 临床肝胆病杂志

ObjectiveTo investigate the clinical features of patients with hepatolenticular degeneration （HLD） aged above 35 years. MethodsA retrospective analysis was performed for the clinical data of the patients with HLD， aged above 35 years， who attended West China School of Public Health， Sichuan University， from April 2018 to April 2023， and according to their clinical symptoms， they were divided into mixed type group with 13 patients， liver type group with 12 patients， and brain type group with 5 patients. Related data were collected， including general information （sex， clinical manifestation， age at confirmed diagnosis， time from initial symptoms to confirmed diagnosis， and family history）， laboratory examination （routine blood test， liver and renal function， serum copper， serum ceruloplasmin， urinary copper， and coagulation function）， and radiological examination. A one-way analysis of variance was used for comparison of normally distributed continuous data between multiple groups， and the Kruskal-Wallis H test was used for comparison of non-normally distributed continuous data between multiple groups； the Fisher’s exact test was used for comparison of categorical data between groups. ResultsFor the 30 patients with HLD， the male/female ratio was 3∶1， and the mean age was 46.13±5.88 years； the patients with positive Kayser-Fleischer ring of the cornea accounted for 43.33%， and the patients with liver cirrhosis accounted for 66.67%. There were significant differences between the three groups in globulin， albumin/globulin ratio， alanine aminotransferase， prothrombin time， international normalized ratio， and activated partial thromboplastin time （F=5.893， 4.513， 4.424， 5.029， 5.248， and 4.942， all P<0.05）. ConclusionMost patients are male among the patients diagnosed with HLD after 35 years of age， with the main clinical types of mixed type and liver type， and such patients tend to have poor liver and coagulation functions. For unexplained liver function abnormalities and liver cirrhosis in this age group， the indicators such as serum ceruloplasmin and urinary copper should be screened as early as possible， and liver and kidney function and coagulation function should be monitored.

Manganese Associated with Non-Wilsonian Hepatolenticular Degeneration as a Rare Cause of Encephalopathy: Case Report

Aim: To describe the clinical picture, diagnosis, and treatment of a patient with encephalopathy as a manifestation of manganese-induced non-Wilsonian hepatolenticular degeneration (NWHD) in a high-complexity care center in a Latin American country. Case description: A 55-year-old male patient from the United States with a history of liver disease associated with alcohol consumption was admitted to the emergency department due to diarrhea, hematemesis, and psychomotor agitation. During his stay, his state of consciousness deteriorated, requiring orotracheal intubation. In his diagnostic study, cerebrospinal fluid tests were negative for infectious etiologies; the endoscopic examinations showed no marks of portal hypertension bleeding, while ammonium and tests for metabolic causes were normal. However, areas of hyperintensity in the basal ganglia were documented on brain MRI, with normal ceruloplasmin serum and urine copper levels, which ruled out Wilson's disease and determined the diagnosis of manganese-induced NWHD. Conclusion: NWHD is a rare cause of chronic encephalopathy with clinical manifestations of extrapyramidal symptoms secondary to basal ganglia dysfunction due to severe liver disease. Its diagnosis becomes a challenge, given that manganese deposits produce it, and no biomarkers can establish the level of exposure to this metal. Brain MRI is indispensable in reflecting these deposits in the basal ganglia.

Objetivo: Describir la presentación clínica, el diagnóstico y el tratamiento de un paciente con encefalopatía como manifestación de degeneración hepatolenticular no wilsoniana producida por manganeso, en un centro de alta complejidad de un país latinoamericano. Descripción del caso: Paciente masculino de 55 años, procedente de Estados Unidos, con antecedente de enfermedad hepática asociada con consumo de alcohol, quien ingresó al servicio de urgencias por un cuadro de diarrea, hematemesis y agitación psicomotora. Durante la estancia presentó deterioro en el estado de consciencia, por lo que requirió intubación orotraqueal. En su estudio diagnóstico, las pruebas de líquido cefalorraquídeo fueron negativas para etiologías infecciosas, en los estudios endoscópicos no tenía estigmas de sangrado portal hipertensivo y el amonio y los estudios para causas metabólicas fueron normales. Sin embargo, se documentaron áreas de hiperintensidad en los ganglios de la base en la resonancia magnética cerebral, con niveles de ceruloplasmina sérica y cobre urinario normales, lo que descartó enfermedad de Wilson y definió el diagnóstico de degeneración hepatolenticular no wilsoniana por depósitos de manganeso. Conclusión: La degeneración hepatolenticular no wilsoniana es una causa infrecuente de encefalopatía crónica con manifestaciones clínicas de extrapiramidalismo, secundaria a disfunción de los ganglios de la base por enfermedad hepática grave. Su diagnóstico se convierte en un reto, dado que se produce por depósitos de manganeso y no existen biomarcadores que puedan establecer el nivel de exposición a este metal. La resonancia magnética cerebral juega, por tanto, un papel indispensable al reflejar esos depósitos en los ganglios de la base.

Acidic Environment Induces Pyroptosis of NLRP3 Inflammatory Vesicle-Mediated Nucleus Pulposus Cells Through Up-Regulation of POSTN Expression

SUMMARY: Intervertebral disc degeneration (IVDD) is induced by nucleus pulposus (NP) dysfunction as a result of massive loss of NP cells. It has been reported that the acidic microenvironment of the intervertebral disc (IVD) can induce NP cell pyroptosis, and that up-regulation of periostin (POSTN) expression has a negative effect on NP cell survival. However, the relationship between the acidic environment, POSTN expression level and NP cell pyroptosis is unclear. Therefore, the aim of this study was to explore the relationship between acidic environment and POSTN expression level in NP cells, as well as the effect of POSTN in acidic environment on NP cell pyroptosis. NP cells were obtained from the lumbar vertebrae of Sprague Dawley (SD) male rats. These cells were divided into normal and acidic groups according to whether they were exposed to 6 mM lactic acid solution. And NP cells in the acidic group were additionally divided into three groups: (1) Blank group: no transfection; (2) NC group: cells transfected with empty vector plasmid; (3) sh-POSTN group: cells transfected with sh-POSTN plasmid to knock down the expression level of POSTN. Quantitative real-time PCR (qRT-PCR) and western blot was performed to assess the expression of POSTN at the mRNAand protein levels. CCK8 was used to evaluate cell survival. Western blot, in addition, was performed to examine acid-sensing ion channels (ASIC)-related proteins. And pyroptosis was detected by ELISA and western blot. The expression level of POSTN was significantly increased in NP cells in acidic environment. Knockdown of POSTN expression promoted the survival of NP cells in acidic environment and reduced the protein levels of ASIC3 and ASIC1a in NP cells. Moreover, knockdown of POSTN expression decreased the pyroptosis proportion of NP cells and the levels of pro-inflammatory cytokines interleukin (IL)-1β and IL-18. The levels of pyroptosis-related proteins NLRP3, ASC, cleaved-Caspase-1, and cleaved-GSDMD were also affected by the decreased POSTN expression. The extracellular acidic environment created by lactic acid solution activated NLRP3 inflammatory vesicle-induced caspase-1 to get involved in NP cell pyroptosis by up-regulating POSTN expression.

La degeneración del disco intervertebral (DDIV) es inducida por una disfunción del núcleo pulposo (NP) como resultado de una pérdida masiva de células NP. Se ha informado que el microambiente ácido del disco intervertebral (DIV) puede inducir la piroptosis de las células NP y que la regulación positiva de la expresión de periostina (POSTN) tiene un efecto negativo en la supervivencia de las células NP. Sin embargo, la relación entre el ambiente ácido, el nivel de expresión de POSTN y la piroptosis de las células NP es poco clara. Por lo tanto, el objetivo de este estudio fue explorar la relación entre el ambiente ácido y el nivel de expresión de POSTN en células NP, así como el efecto de POSTN en ambiente ácido sobre la piroptosis de las células NP. Las células NP se obtuvieron de las vertebras lumbares de ratas macho Sprague Dawley (SD). Estas células se dividieron en grupos normales y ácidos según se expusieron a una solución de ácido láctico 6 mM. Las células NP en el grupo ácido se dividieron adicionalmente en tres grupos: (1) Grupo en blanco: sin transfección; (2) grupo NC: células transfectadas con plásmido vector vacío; (3) grupo sh-POSTN: células transfectadas con plásmido sh-POSTN para reducir el nivel de expresión de POSTN. Se realizó una PCR cuantitativa en tiempo real (qRT-PCR) y una transferencia Western para evaluar la expresión de POSTN en los niveles de ARNm y proteína. Se utilizó CCK8 para evaluar la supervivencia celular. Además, se realizó una transferencia Western para examinar las proteínas relacionadas con los canales iónicos sensibles al ácido (ASIC). La piroptosis se detectó mediante ELISA y Western blot. El nivel de expresión de POSTN aumentó significativamente en células NP en ambiente ácido. La eliminación de la expresión de POSTN promovió la supervivencia de las células NP en un ambiente ácido y redujo los niveles de proteína de ASIC3 y ASIC1a en las células NP. Además, la eliminación de la expresión de POSTN disminuyó la proporción de piroptosis de las células NP y los niveles de citocinas proinflamatorias interleucina (IL) - 1β e IL-18. Los niveles de proteínas relacionadas con la piroptosis NLRP3, ASC, Caspasa-1 escindida y GSDMD escindida también se vieron afectados por la disminución de la expresión de POSTN. El ambiente ácido extracelular creado por la solución de ácido láctico activó la caspasa-1 inducida por vesículas inflamatorias NLRP3 para involucrarse en la piroptosis de las células NP mediante la regulación positiva de la expresión de POSTN.

Efficacy of low-vision devices in elderly population with age-related macular degeneration

Purpose: Age?related macular degeneration (AMD) is a common cause of blindness, residual damage to macular area in spite of treatment necessitates visual rehabilitation by means of low?vision aids (LVAs). Methods: Thirty patients suffering from different stages of AMD requiring LVAs were included in this prospective study. Patients with nonprogressive, adequately treated AMD were enrolled over a 12?month period, prescribed requisite LVAs and followed?up for a minimum 1?month period. Before and after provision of LVAs, near work efficiencies were evaluated by calculating reading speed as words per minute (wpm) under both photopic and mesopic light conditions, and impact of poor vision on activities of daily living (ADL) was quantified by modified standard questionnaire based on Nhung X et al. questionnaire. Results: Of the 30 patients mean studied with mean age of 68 ± 10 years, 20 patients (66.7%) had dry AMD in better eye and 10 (33.3%) had wet AMD. Post?LVA, near visual acuity improved significantly and all cases were able to read some letters on near vision chart with an average improvement of 2.4 ± 0.96 lines. The different LVAs prescribed were high plus reading spectacles (up to 10 D) in 23.3%, hand?held magnifiers in 53.3%, base in prisms in 10%, stand held magnifiers in 6.7%, and bar and dome magnifiers in 3.3%. Conclusion: LVAs are effective in visual rehabilitation in patients with AMD. Self?reported reduction in visual dependency and improvement in vision?related quality of life post use of aids corroborated perceived benefit.

The Clinical Outcome of Brolucizumab in the Treatment of Neovascular Age-Related Macular Degeneration – A Prospective Observational Study

Background: Neovascular age-related macular degeneration (nAMD), also known as wet AMD, is a chronic eye disease that affects the macula, which is the central part of the retina responsible for sharp, central vision. Brolucizumab is a type of anti-vascular endothelial growth factor (VEGF) drug, which works by blocking the activity of a protein called VEGF that promotes the growth of abnormal blood vessels under the macula in neovascular AMD. The aim of this study was to evaluate the clinical outcome of brolucizumab in the treatment of neovascular age-related macular degeneration. Material & Methods: This prospective observational study was conducted in Department of Ophthalmology, Bangladesh Eye Hospital & Institute Ltd, Dhaka, Bangladesh, during the period from February 2022 to February 2023. Total 60 patients with neovascular AMD were included in this study who were treated with brolucizumab. Results: The mean age of the patients was 74.3 (SD±9.8) years. Majority of the study subjects were (51.7%) female patients in the study. In our study, majority (38.3%) of the patients had only their right eye affected. In optical coherence tomography (OCT) findings, we found that a high percentage of patients had subretinal fluid (85%), intraretinal fluid (61.7%), and sub-RPE fluid (83.3%). The BCVA showed a significant change after 12 weeks of treatment, as indicated by the P-value of 0.0007. Here improvement of vision was seen in patients with AMD with active Choroidal neovascularization (CNV). But in case of AMD with macular scar, no improvement of vision was seen. In addition, the SRT, FCP, and CMT parameters also showed a statistically significant (P<0.001) improvement after brolucizumab treatment. In our study, 4 patients (6.7%) experienced intraocular inflammation, which is inflammation within the eye, 2 patients (3.3%) reported cloudy vision, and 3 patients (5%) experienced eye redness as a complication of the treatment. The majority of the patients, 51 (85%) did not experience any complications from the treatment. After treatment, improved vision was seen in most of the study patients (70%) and 30% had no improvement. Conclusion: From the findings of our study, it can be concluded that brolucizumab may be an effective treatment for neovascular AMD, as it can improve the best-corrected visual acuity and structural outcomes of the retina such as subfoveal retinal thickness, foveal center point, and central macular thickness. There was also a tolerable complication rate after treatment.

Degeneración combinada subaguda

Introducción: La degeneración combinada subaguda (DCS) es un trastorno caracterizado por la degeneración difusa de la sustancia blanca a nivel del SNC, que afecta específicamente los cordones posteriores y laterales de la médula espinal, con pérdida de la mielinización periférica y central. De manera frecuente, las manifestaciones clínicas son parestesias y debilidad generalizada causada por deficiencia de vitamina B12. Presentación del caso: Paciente masculino de 79 años, con cuadro clínico de 3 meses de evolución de limitación funcional para la marcha acompañado de desorientación. Al examen físico evidenció desorientación, cuadriparesia e hiporreflexia, con niveles séricos bajos de vitamina B12, RM cervical con focos hiperintensos en el segmento C3/C6 y endoscopia de vías digestivas altas con atrofia de la mucosa gástrica. Presentamos un caso clínico de DCS. Discusión: Este es un caso de DCS que se manifiesta por medio de una alteración neuropsiquiátrica, con una presentación inicial inespecífica que comprende deterioro de la marcha, movimientos anormales con afectación cognitiva y psiquiátrica dada por alucinaciones visuales y desorientación. Su sospecha es importante en pacientes con factores de riesgo por medio del conocimiento de la patología, para una adecuada sospecha diagnóstica y una instauración oportuna de reposición vitamínica, la cual presenta una excelente respuesta. Conclusión: La DCS es un trastorno en el que se evidencia anemia con deficiencia de vitamina B12, des-mielinización del tejido nervioso y en muchos casos signos sugestivos de atrofia gástrica, y para ello es crucial la detección temprana de esta enfermedad por medio de la determinación de niveles séricos de vitamina B12, asociado a síntomas neurológicos, para así lograr su adecuado diagnóstico y tratamiento.

Introduction: Subacute combined degeneration (DCS) is a disorder characterized by diffuse degeneration of white matter at the CNS level, specifically affecting the posterior and lateral cords of the spinal cord, also with loss of peripheral and central myelination, frequently the clinical manifestations are paresthesias and generalized weakness caused by vitamin B12 deficiency. Case presentation: A 79-year-old male patient with a 3-month history of functional limitation for walking accompanied by disorientation. On physical examination, he revealed disorientation, quadriparesis, and hyporeflexia, with low serum levels of vitamin B12, cervical MRI with hyperintense foci in segment C3/C6, and upper digestive tract endoscopy with atrophy of the gastric mucosa. We present a clinical case of DCS. Discussion: This is a case of DCS that manifests itself through neuropsychiatric alteration with a nonspecific initial presentation with gait impairment, abnormal movements with cognitive and psychiatric affectation given by visual hallucinations and disorientation. Its suspicion is important in patients with risk factors. risk through knowledge of the pathology for an adequate diagnostic suspicion and a timely establishment of vitamin replacement for which it presents an excellent response. Conclusion: DCS is a disorder where anemia with vitamin B12 deficiency, demyelination of the nervous tissue and in many cases signs suggestive of gastric atrophy are evident, for which early detection of this disease is crucial through the determination of serum levels of vitamin B12 associated with neurological symptoms, in order to achieve its proper diagnosis and treatment.

Desprendimiento de la capa bacilar de la retina asociado a enfermedad inflamatoria ocular

El desprendimiento de la capa bacilar de la retina es la separación de los segmentos internos de los fotorreceptores del resto de la retina neurosensorial, o separación entre la zona miode y elipsoide de la retina, que en un hallazgo reciente se puede identificar mediante la tomografía de coherencia óptica de dominio espectral. El objetivo es actualizar los conocimientos sobre el desprendimiento de la capa bacilar de la retina y el uso de la tomografía de coherencia óptica de dominio espectral en las enfermedades oculares que están asociadas con este signo. Se consultaron las fuentes bibliográficas como Google académico, SciELO LAC, Medline y MEDICARIBE. Se limitaron los resultados al idioma español e inglés y a los últimos cinco años. Se recuperaron 54 documentos, de ellos 18 resultaron relevantes a esta investigación. Los autores más mencionados fueron Ramtohul, Metha y Cicinelli. Ellos trabajaron el signo clínico en cuestión y reportaron la experiencia en la atención a los pacientes aquejados con esta enfermedad ocular. El desprendimiento de la capa bacilar de la retina es un signo presente en varias enfermedades asociadas a inflamación del segmento posterior ocular. La tomografía de coherencia óptica de dominio espectral es una técnica efectiva para determinarlo, aunque estos planteamientos aún son escasos en la literatura, lo cual reafirma la importancia científica de continuar los estudios a partir de hipótesis iniciales desde el punto de vista histológico y tomográfico.

Retinal bacillary layer detachment is the separation of the inner segments of the photoreceptors from the rest of the neurosensory retina, or separation between the myode and ellipsoid zone of the retina, which in a recent finding can be identified by spectral-domain optical coherence tomography. The objective is to update the knowledge about the detachment of the bacillary layer of the retina and the use of spectral-domain optical coherence tomography in ocular diseases that are associated with this sign. Bibliographic sources such as academic Google, SciELO LAC, MEDLINE and MEDICARIBE were consulted. Fifty-four documents were retrieved, of which 18 were relevant to this research. The results were limited to the Spanish and English language and to the last five years. The most mentioned authors were Ramtohul, Metha and Cicinelli. They worked on the clinical sign in question and reported the experience in caring for patients afflicted with this ocular disease. Detachment of the bacillary layer of the retina is a sign present in several diseases associated with ocular posterior segment inflammation. Spectral-domain optical coherence tomography is an effective technique to determine it, although it is still scarce in the literature, which reaffirms the scientific validity of continuing studies from initial hypotheses from the histological and tomographic point of view.

The nuclear factor E2-related factor 2 and age-related macular degeneration / O fator 2 relacionado a NF-E2 e a degeneração macular relacionada à idade

ABSTRACT After the discovery of anti-vascular endothelial growth factor agents as treatment of wet age-related macular degeneration, the number of studies with the objective to understand the molecular mechanisms involved in the age-re lated macular degeneration genesis has increased. The importance of the nuclear factor e2-related factor 2 lies in its activation-derived proteins being involved in the maintenance of the redox balance and consequent prevention of degenerative macular disease. This article aims to present the characteristics of nuclear factor e2-related factor 2 and describe the main nuclear factor e2-related factor 2-activated antioxidant enzymes that contribute to the preservation of vision.

RESUMO Após a descoberta do anti fator de crescimento en dotelial vascular no tratamento da degeneração macular relacionada à idade úmida, muitas pesquisas têm sido realizadas com o intuito de elucidar os mecanismos moleculares envolvidos na gênese da degeneração macular relacionada à idade. O fator nuclear eritroide 2 relacionado ao fator 2 destaca-se pelo fato de diversas proteínas, oriundas de sua ativação, estarem envolvidas na manutenção do equilíbrio do estado redox e consequente prevenção da doença macular degenerativa. Este artigo mostra as características do fator nuclear eritroide 2 relacionado ao fator 2 e descreve as principais enzimas antioxidantes originadas da ativação que contribuem para a preservação da visão.

Baseline predictors of short-term visual outcomes after intravitreal conbercept injection for neovascular age-related macular degeneration / Preditores iniciais de desfechos visuais de curto prazo com injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade

ABSTRACT Purpose: Neovascular age-related macular degeneration is the leading cause of vision loss in the elderly. We aimed to identify baseline predictors of visual prognosis after intravitreal conbercept injection for neovascular age-related macular degeneration. Methods: We conducted a retrospective review of 58 patients with neovascular age-related macular degeneration who were treated with intravitreal injections of conbercept 0.5 mg in routine clinical practice. Basic information such as age, sex, intraocular pressure, and disease course was collected. Best-corrected visual acuity, mean retinal sensitivity, and optical coherence tomography findings were recorded at baseline and 6 months after treatment. Logistic regression analysis was used to identify independent predictors of best-corrected visual acuity at 6 months after treatment. Results: After the 6-month treatment, the mean best-corrected visual acuity improved from 1.10 ± 0.42 logarithm of the minimum angle of resolution (logMAR) to 0.41 ± 0.18 logMAR, the mean retinal sensitivity increased from 5.13 ± 0.86 dB to 7.32 ± 1.21 dB, the mean central retinal thickness decreased from 440.38 ± 61.05 μm to 260.01 ± 24.86 μm, and the total number of hyperreflective dots and the number of hyperreflective dots in each retina layer were significantly reduced as compared with those before treatment (all p<0.05). Twenty-two patients showed improved vision, and 36 had unimproved vision. Multivariate analyses revealed that the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age were independent predictors of best-corrected visual acuity (all p<0.05). Conclusion: Poor recovery of patients after intravitreal conbercept injection may be related to the number of subretinal hyperreflective dots, the state of external limiting membrane, baseline best-corrected visual acuity, and age, which may be used as predictors of short-term visual outcomes and should be fully evaluated before operation.

RESUMO Objetivo: A degeneração macular neovascular relacionada à idade é a principal causa de perda de visão em idosos. O objetivo deste estudo foi identificar os preditores iniciais que afetam o prognóstico visual após a injeção intravítrea de combercepte para degeneração macular neovascular relacionada à idade. Métodos: Esta é uma revisão retrospectiva de 58 pacientes com degeneração macular neovascular relacionada à idade que foram tratados com injeções intravítreas de 0,5 mg de combercepte na prática clínica de rotina. Foram coletadas informações básicas, tais como idade, sexo, pressão intraocular e evolução da doença. A melhor acuidade visual corrigida, as sensibilidades retinianas médias e varreduras de tomografia de coerência óptica foram registradas no início do estudo e 6 meses após o tratamento. Foi efetuada uma análise de regressão logística para determinar os preditores independentes da melhor acuidade visual corrigida 6 meses após o tratamento. Resultados: Após 6 meses de tratamento, a média da acuidade visual melhor corrigida melhorou de 1,10 ± 0,42 para 0,41 ± 0,18 logMAR; as sensibilidades retinianas médias aumentaram de 5,13 ± 0,86 para 7,32 ± 1,21 dB; a espessura retiniana central média diminuiu de 440,38 ± 61,05 para 260,01 ± 24,86 μm; e os pontos hiper-reflexivos, tanto em números totais quanto em cada camada de retina, foram significativamente reduzidos em comparação com os valores de antes do tratamento (todos com p<0,05). Houve 22 pacientes com visão melhorada e 36 pacientes com visão não melhorada. As análises multivariadas mostraram que o número de pontos hiper-reflexivos sub-retinianos, o estado da membrana limitante externa, a melhor acuidade visual corrigida inicial e a idade foram preditores independentes para a melhor acuidade visual corrigida (todos com p<0,05). Conclusão: A má recuperação de pacientes após a injeção de combercepte intravítreo pode estar relacionada ao número de pontos hiper-reflexivos sub-retinianos, ao estado da membrana limitante externa, à acuidade visual corrigida inicial e à idade, parâmetros que podem ser usados como preditores de resultados visuais de curto prazo e devem ser totalmente avaliados antes da cirurgia.

Degenerated broad ligament fibroid mimicking ovarian cyst: A case report

The commonest diagnosis of a cystic mass in the pelvis is ovarian cyst, here we report a case of cystic degeneration of broad ligament fibroid mimicking as a ovarian cyst. A 45-year-old lady presented with abdominal discomfort. On evaluation, a pelvic mass of 20 weeks size of varying consistency was noted. Ultra sonogram and Magnetic Resonance Imaging gave a differential diagnosis of right sided broad ligament fibroid and ovarian cyst. Anticipating possible ovarian mass owing to its size, laparotomy was performed and noted a large false broad ligament fibroid which has undergone cystic degeneration. Total abdominal hysterectomy and bilateral salpingo-oopherectomy was performed, however a differential diagnosis of ovarian mass should always be made before surgery.

The postoperative adjacent segment degeneration between the microscopically anterior cervical discectomy with fusion and anterior cervical corpectomy with fusion in the treatment of cervical spondylotic myelopathy and the influencing factors analysis of / 中国医师进修杂志

Objective:To compare the postoperative adjacent segment degeneration (ASD) between the microscopically anterior cervical discectomy with fusion (ACDF) and anterior cervical corpectomy with fusion (ACCF) in the treatment of cervical spondylotic myelopathy and its influencing factors.Methods:Fifty patients with cervical spondylotic myelopathy treatment in the Qinzhou Second People′s Hospital from July 2018 to July 2020 were selected, they were divided into two groups, 25 patients performed ACDF (ACDF group), and 25 patients performed ACCF (ACCF group). The perioperative period, efficacy and incidence of ASD were compared between the two groups, and the influencing factors of ASD were analyzed.Results:The intraoperative blood loss, operation time, length of hospital stay and postoperative drainage in ACCF group were higher than those in ACDF group: (58.34 ± 8.61) ml vs. (46.77 ± 7.24) ml, (99.57 ± 10.72) min vs. (86.14 ± 9.64) min, (8.97 ± 1.43) d vs. (7.56 ± 1.24) d, (17.92 ± 2.95) ml vs. (14.28 ± 2.66) ml, there were statistical differences ( P<0.05). The postoperative Japanese Orthopaedic Association (JOA) scores and Neck Disability Index (NDI) scores in the two groups were improved significantly ( P<0.05), but the scores of JOA and NDI in the two groups had no significant differences ( P>0.05). The incidence of ASD in the two groups had no significant differences ( P>0.05). The Cox univariate analysis showed that age >59 years, intervertebral disc degeneration, number of fusion segments >2, osteoporosis and postoperative ASD were risk factors for ASD( P<0.05). Conclusions:The effect of microscopically ACDF is similar to that of ACCF in the treatment of cervical spondylotic myelopathy, but ACDF has the advantages of less trauma and quick recovery. The risk of postoperative ASD should be vigilant for patients with age >59 years old, intervertebral disc degeneration, number of fusion segments >2 or osteoporosis.

Research progress of mitochondrial genetics in age-related macular degeneration / 中华实验眼科杂志

Mitochondria are the center of cellular energy metabolism, and their functions are tightly regulated by the nuclear and mitochondria genomes.Potential mechanisms responsible for age-related mitochondrial dysfunction include the accumulation of mitochondrial DNA (mtDNA) damage caused by replication errors or oxidative damage, and the epigenetic changes in mtDNA (mitoepigenetics). These mechanisms are essential for the development and progression of age-related macular degeneration (AMD). Age-related mtDNA damage disrupts energy metabolism and cellular function in the retinal pigment epithelium (RPE) and neuroretinal cells, which further mediates oxidative stress, lysosomal dysfunction and pyroptosis, resulting in RPE degeneration, drusen deposition and retinal inflammation.Mitochondrial genome protection, such as humanin administration, may be a promising preventive or therapeutic target in the early stages of AMD.This review focused on the research progress of the mitochondrial genetic mechanism in AMD pathogenesis and provided new ideas for exploring the prevention and treatment strategies of AMD.

Association of the occurrence of reticular macular diseases with chronic kidney disease based on estimated glomerular filtration rate / 中华实验眼科杂志

Objective:To analyze the relationship between reticular macular disease (RMD) and chronic kidney disease (CKD) by estimated glomerular filtration rate (eGFR).Methods:A cross-sectional study was conducted.Thirty-six consecutive patients (71 eyes) with subretinal drusenoid deposits in at least one eye in optical coherence tomography (OCT) images were enrolled as the RMD group, and 29 consecutive patients (50 eyes) with age-related macular degeneration (AMD) in at least one eye were identified as the non-RMD group at the First Affiliated Hospital of Guangzhou Medical University from February to September 2019.In the same period, 32 healthy volunteers (64 eyes) without eye disease were included as the healthy control group.Serum was collected to calculate the estimated creatinine clearance (eCcr) and the eGFR.The choroidal thickness of macular fovea and the flow density of choroidal capillary layer were measured by OCT.The related factors of RMD and the correlation between CKD and RMD were analyzed by multiple logistic regression analysis.The relationship between eGFR and choroidal capillary blood flow density and foveal choroidal thickness in RMD patients was analyzed by Pearson linear correlation analysis.This study adhered to the Declaration of Helsinki.The study protocol was approved by the Ethics Committee of the First Affiliated Hospital of Guangzhou Medical University (No.2022-50)Results:The eGFR value of the RMD group was (66.40±27.58)ml/(min·1.73 m 2), which was significantly lower than (84.40±20.91)ml/(min·1.73 m 2) of the non-RMD group and (87.64±22.32)ml/(min·1.73 m 2) of the healthy control group (both at P<0.01). eGFR was significantly correlated with the occurrence of RMD ([odds ratio, OR]=0.973, 95%[confidence interval, CI]: 0.954-0.992, P=0.005). Subgroup analysis showed that this correlation was significant in the CKD stage (eGFR<60 ml/[min·1.73 m 2]) ( OR=6.482, 95% CI: 1.543-27.236, P=0.011). The choroidal thickness of the macular fovea in the RMD group was significantly lower than that of the non-RMD grup and healthy control group (both at P<0.01). In the RMD group, no significant correlation was found between the choroidal thickness of the macular fovea and eGFR ( r=0.138, P>0.05), and the flow density of choroidal capillary layer was moderately positively correlated with eGFR ( r=0.457, P<0.05). Conclusions:There is a correlation between the occurrence of CKD and RMD, which may be due to the confounding effect of the systemic microcirculation disorder.

Inhibitory effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization and its mechanism / 中华实验眼科杂志

Objective:To study the effect of ranibizumab on retinal oxidative stress in a rat model of choroidal neovascularization (CNV) and its mechanism.Methods:Sixty SPF male SD rats aged 10 weeks were randomly divided into normal control group, model control group, ranibizumab group, nuclear factor erythroid 2-related factor 2 (Nrf2) inhibitor (ML385) group, ranibizumab+ ML385 group, with 12 rats in each group according to a random number table.Except for the normal control group, the CNV model was established in the other four groups via krypton laser induction.According to grouping, the ranibizumab group, ML385 group and ranibizumab+ ML385 group were intravitreally injected with 1 μl of ranibizumab, ML385 and ranibizumab+ ML385, respectively.Model control group and normal control group received an intravitreal injection of normal saline of equal volume.The CNV area was measured through choroidal wholemounts.Pathological change of the retina was observed by hematoxylin and eosin staining.Expressions of Nrf2, superoxide dismutase (SOD) and quinone oxidoreductase 1 (NQO1) were detected using Western blot and real-time PCR.The use and care of animals complied with laboratory animal welfare guidelines.The study protocol was approved by the Laboratory Animal Welfare and Ethics Committee of Tengzhou Central People's Hospital (No.JN.No20210214S1200430[121]).Results:CNV areas of the model control group, ML385 group and ranibizumab+ ML385 group were (23.01±1.52)×10 3, (30.23±2.01)×10 3 and (18.56±1.85)×10 3 μm 2, respectively, which were significantly higher than (12.35±1.22)×10 3 μm 2 of ranibizumab group (all at P<0.001). The CNV area of ranibizumab+ ML385 group was smaller than that of model control group and ML385 group, and the CNV area of ML385 group was larger than that of model control group, showing statistically significant differences (all at P<0.001). Hematoxylin and eosin staining showed that the structural damage of the retinal pigment epithelium-choroid-sclera complex was slighter in ranibizumab group than model control group, severer in ranibizumab+ ML385 group than ranibizumab group but slighter than model control group, severer in ML385 group than model control group.The mRNA and protein expressions of Nrf2, SOD and NQO1 of ranibizumab group were lower than those of normal control group but higher than those of model control group, ML385 group and ranibizumab+ ML385 group, and the differences were statistically significant (all at P<0.05). The mRNA and protein expressions of Nrf2, SOD and NQO1 were higher in ranibizumab+ ML385 group than model control group and ML385 group, showing statistically significant differences (all at P<0.05). Conclusions:Ranibizumab can inhibit the growth of CNV induced by krypton laser and reduce RPE damage caused by retinal oxidative stress.The mechanism is related to the activation of Nrf2/ARE pathway.

Progress of diagnosis and treatment for degenerative cervical myelopathy / 国际外科学杂志

Degenerative cervical myelopathy (DCM) is a kind of disease caused by cervical spinal cord compression and injury due to cervical degeneration. With the increasing of aging population in China, the incidence of DCM is also increasing year by year. The pathogenesis of DCM includes static degeneration and dynamic instability. The clinical manifestations of DCM are mainly symptoms and signs of cervical spinal cord dysfunction. Magnetic resonance imaging (MRI), especially some advanced quantitative microstructural MRI, plays an important role in the early diagnosis of DCM. Conservative treatment of DCM patients is often ineffective, and most patients need surgery to relieve nerve compression, and the surgical approach selection is still controversial. The long duration of symptoms, poor preoperative neurological status and advanced age were the main factors that caused the poor postoperative outcome. This article mainly reviews the recent research progress on the incidence, pathogenesis, diagnosis, evaluation and treatment of DCM.

The Action Effect of Two Kinds of Lumbar Massage Obliquity Manipulation with Different Lumbar Degeneration Degrees: A Comparative Study / 医用生物力学

Objective To compare the action effect of traditional and modified lumbar massage obliquity manipulation with different degrees of lumbar degeneration. Methods The biomechanical model of quality-spring-damping system lumbar spine was established and massage forces from professional massage doctors were collected. The force was used as input of the model, and lumbar degeneration was simulated by increasing elastic coefficient of the spring and damping coefficient of the damping in the model. By using MATLAB/ Simulink simulation technology, the effects of massage obliquity manipulation ( the maximum relative displacement and maximum acceleration) with different degrees of lumbar degeneration were obtained for comparative analysis.Results When the lumbar spine was degenerative, the maximum relative displacement and maximum acceleration of each segment were obtained under two manipulations. With the increase of lumbar degenerationdegree, the maximum relative displacement and maximum acceleration of each segment under two manipulations showed a downward trend, and the attenuation rate of the maximum relative displacement and maximum acceleration of each segment under two manipulations was obtained. Conclusions When degenerative changes in the spine do not occur, the effectiveness of traditional lumbar massage obliquity manipulation is slightly better than that of modified lumbar massage obliquity manipulation, but the safety of modified lumbar massage obliquity manipulation is obviously better than that of the traditional lumbar massage obliquity manipulation, so the modified lumbar massage obliquity manipulation should be used. With the aggravation of lumbar degeneration, the action effects of two manipulations are attenuated in a power function. The attenuation rate of effectiveness of modified lumbar massage obliquity manipulation is significantly faster than that of traditional lumbar massage obliquity manipulation, indicating that the modified lumbar massage obliquity manipulation should not be used in the caseof lumbar degeneration.

Research progress of novel bispecific monoclonal antibody Faricimab in the treatment of diabetic macular edema and age-related macular degeneration / 国际眼科杂志(Guoji Yanke Zazhi)

Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.